SPECIALIZED COOPERATIVE CENTERS PROGRAM IN REPRODUCTION RESEARCH
RELEASE DATE: September 27, 2002
RFA: HD-02-029
National Institute of Child Health and Human Development (NICHD)
(http://www.nichd.nih.gov)
LETTER OF INTENT RECEIPT DATE: May 21, 2003
APPLICATION RECEIPT DATE: June 18, 2003
THIS RFA CONTAINS THE FOLLOWING INFORMATION
o Purpose of this RFA
o Research Objectives
o Mechanism of Support
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations
PURPOSE OF THIS RFA
The National Institute of Child Health and Human Development (NICHD), through
the Reproductive Sciences Branch (RSB) in the Center for Population Research
(CPR), provides funding for a limited number of research centers in the
reproductive sciences. These centers provide an arena for multidisciplinary
interactions among basic and clinical scientists interested in establishing
high quality research programs in the reproductive sciences. Accordingly,
the purpose of this RFA is to announce the annual recompetition of the
Specialized Cooperative Centers Program in Reproduction Research.
Applications are sought from investigators willing to participate with the
NICHD under a cooperative agreement in a multicenter cooperative research
program. Center investigators will be expected to work with NICHD staff in
facilitating research collaborations and interactions within and between
centers. Such a cooperative program will form a national network that
fosters communication, innovation, and research excellence with the ultimate
goal of improving human reproductive health through accelerated transfer of
basic science findings into clinical practice.
RESEARCH OBJECTIVES
Background
The ultimate goal of biomedical research supported by the RSB is to develop
new knowledge leading to clinical applications that will enable men and women
to control their own fertility choices with methods that are safe, effective,
inexpensive, reversible, and acceptable to various population groups. Such
research aims to develop new leads for contraception, procedures for
alleviating infertility, and fertility-preserving treatments for reproductive
disorders that threaten fertility.
The present day need for the availability of contraceptive options acceptable
to diverse populations remains globally unmet. Among the 600 million women
of reproductive age in today"s world, as many as 228 million women are at
risk of unintended pregnancy. Up to 64 percent of all worldwide pregnancies
are unintended (mistimed or completely unwanted). Over 50 million abortions
occur worldwide each year with minimal estimates of at least 100,000
abortion-related deaths annually. In the U.S., three million unintended
pregnancies--57 percent of all pregnancies--occur annually, with half
resulting in abortion as an outcome. In half of the 1.3 million abortions
occurring in the U.S. each year, a contraceptive method being used failed to
prevent pregnancy.
Families, family values, and family planning form the cultural essence and
cohesiveness of our existence as human societies. One of the most basic of
human rights--the right to procreate--is frustrated or denied by the
occurrence of infertility in a couple desiring children. It has been
estimated that infertility affects between 37 and 70 million married couples
around the world. In U.S. studies described nearly 50 years ago, it was
stated that up to 10 percent of married couples were "sterile," with the
remaining 90 percent having varying degrees of fertility. More recent and
technically rigorous U.S. survey studies have conservatively identified that
there are about 2.3 million infertile couples, which is about nine percent of
the domestic married couple population base with wives aged 15-44. In
addition, such studies found that about 4.9 million U.S. women in this age
range had an impaired ability to have children. At least 30-50 percent of
infertility is attributable to male factor infertility for which the
pathophysiology is either not understood at all or, at best, poorly
understood. The prognosis for male infertility treatment outcomes is
extremely poor at present. Indeed, whereas 80 percent of infertile women can
be successfully treated, male infertility can be treated in only 10-20
percent of such men. However, the widespread use of assisted reproductive
technologies such as intracytoplasmic sperm injection (ICSI) and its variants
have enabled otherwise infertile men to father children, although possible
genetic causes of the infertility are likely transmitted to the progeny.
While analyses of the U.S. population base have not found alarming annual
increases in the overall number of infertile couples or the overall
prevalence of infertility, significant age-related increases in infertility,
coupled with delayed childbearing in the contemporary couple population base,
have been found in such studies. Physician office visits reflecting current
societal life style requirements for infertility services have markedly
increased in the U.S. from 1968 (600,000) to 1988 (1,350,000) and are
estimated to approach two million visits in 2000. Of the infertile couples
seeking treatment for infertility, it has been estimated that up to one-half
will be unsuccessful in achieving their desired outcome. In concert with the
increased medical assistance sought, U.S. infertility service costs have
risen to exceed a billion dollar annual medico-economic impact in the U.S.
Reproductive disorders affecting fertility are associated with significant
morbidity and a degree of mortality in some specific instances that cannot be
ignored. During the past two decades, the incidence of ectopic pregnancy has
increased from 4.5 to 16.1 per 10,000 pregnancies. The rate appears to be
increasing particularly in young women aged 15-19, perhaps in relationship to
the U.S. factors of earlier age of menarche and initiating sexual activity
leading to encountering tubal disease factors earlier. In 1989, it was
reported that 88,400 women experienced an ectopic pregnancy and 34 of them
died as a direct consequence. While improved diagnostic procedures and early
intervention protocols have resulted in markedly reducing mortality,
surviving women are left with an eight-fold risk of reoccurrence and a 20
percent lowered chance of ever conceiving again.
Accompanying the human costs of morbidities of reproductive tract disorders,
as noted above, are the attendant substantial costs to the U.S. health care
system involving the diagnosis, treatment, and follow-up services provided to
the patients, as well as the added costs to the patient and the U.S. economy
of lost employment and family service hours. In reproductive age couples,
the obstructive sequelae of male accessory gland infections account for eight
to 12 percent of male partner diagnostic costs for fertility impairment. In
reproductive age females, it has been estimated that the general incidence of
endometriosis is five to 15 percent. The incidence of endometriosis in
females being surgically treated for infertility is known to be 30 to 50
percent. Among infertile females with no other known cause of their
infertility, the incidence of endometriosis has been reported to be 40 to 70
percent. A diagnosis of severe endometriosis often leads to
hysterectomy-associated treatment. While the causative role of endometriosis
in infertility remains poorly understood and its optimal diagnosis and
treatment remain a goal--not an accomplishment--of contemporary medicine, the
morbid impact of the associated pelvic pain has significant human cost as
well as national economic costs.
Similarly, the role of dysfunctional uterine bleeding, either in the presence
or the absence of uterine leiomyomata (fibroids), is not well understood
despite its common occurrence and decades of research. It is a significant
factor in noncompliant contraceptive use or discontinuance and, therefore, in
the unintended pregnancy problem. Uterine myomata occur in nearly 20 percent
of all reproductive age women, are the single most common diagnosis in
gynecological hospital admissions, may be the only abnormality observed in an
infertile couple, and represent the most common medical indication for an
unintended and often unwanted hysterectomy that prematurely ends a female"s
reproductive options.
Polycystic ovary syndrome (PCOS) is a major cause of female infertility, as
well as other reproductive system, and other tissue and organ system
morbidities. Identified more than 60 years ago by Stein and Leventhal, the
etiology of PCOS remains misunderstood despite 60 years of research. This
insidious disease is currently the most common endocrine disorder of women of
reproductive age. Recent prevalence rate estimates suggest that between five
and 10 percent of the reproductive age population of U.S. women suffers the
full-blown syndrome of hyperandrogenism, chronic anovulation, and polycystic
ovaries. Also poorly understood is the pathogenesis of premature ovarian
failure that affects one in 100 women by age 40. Interestingly, 16 percent
of women carrying the fragile X pre-mutation present with premature ovarian
failure.
It is becoming increasingly apparent that some conditions of male and female
infertility may be genetically based. In males, there is considerable
evidence from breeding studies and gene knockout experiments in animals that
mutation of over 100 separate genes results in infertility. More limited
studies in humans show that a number of inherited diseases are associated
with abnormal sperm morphology and function. These data suggest that a
significant number of men with infertility may have one or more mutations
that predispose to their condition. However, it is currently not possible to
determine which men have genetic infertility. Similarly, it is estimated
that 15-20 percent of human pregnancies are chromosomally abnormal as a
result of division errors during oocyte meiosis or early embryonic cleavage.
Such errors not only are the leading cause of birth defects, but also may be
the single most important factor contributing to human infertility.
Recognizing that the interactive needs of basic and clinical research
necessary to address the above and related problems may be so complex that
they cannot be solved by individual investigators working alone without the
intellectual and fiscal resources of a cooperative specialized center
program, it is the intention of the RSB, contingent upon the availability of
funds, to continue and maintain organized, multi-component reproductive
extramural research programs of high quality that focus on topics of high
priority and significance because of their critically important relationship
to the mission of the RSB.
Objectives
The objectives of this Centers Program are to support specialized
reproductive research programs of high quality, and to facilitate and
accelerate bidirectional transfer of knowledge between the laboratory and
clinic. This RFA is specifically designed to stimulate the reproductive
sciences research community to organize and maintain research-based centers
of outstanding quality that, serving as national research resources, form a
cooperative network with NICHD that fosters communication, innovation, and
high quality reproductive research. Such networking as afforded by the
cooperative nature of this Centers Program will ensure that the reproductive
research community remains in the forefront of the development and
utilization of new technologies that can be used to diagnose, treat, and
ameliorate reproductive disorders, as well as to identify novel leads for
fertility regulation.
Research Scope
The Specialized Cooperative Centers Program in Reproduction Research (SCCPRR)
is composed of research-based center grants designed to support interactive
groups of research projects and supporting core service facilities. The
research activities included in these center grants must comprise, by
definition, a multidisciplinary approach to biomedical problems addressing
the specific research topic areas announced in this RFA (see below). These
centers may have more than one theme, focus or emphasis, but all of the
subprojects involved must be responsive to one or more of the specific
research areas of reproduction supported by the RSB. Furthermore, the
translational objective of this Program requires that one of the subprojects
be entirely or predominantly clinical.
The following is a list of topics that are considered to be responsive to the
research mission areas of the RSB. Additionally, these topics identify areas
where research at the basic/clinical interface is deemed essential to the
potential development of new leads or approaches to fertility regulation, as
well as of diagnostic tools and procedures for the detection, treatment, and
effective management of reproductive disorders that impact on reproductive
competence.
o Reproductive Developmental Biology -- origins and differentiation of germ
cells, the endocrine, paracrine, and physiologic mechanisms involved in
gametogenesis, including germ cell-somatic cell interactions, germ cell
proliferation and apoptosis, and germ cell transplantation, fertilization,
including sperm motility and capacitation, zona pellucida binding, and
mechanisms to block polyspermy, pre-implantation embryonic development
including zygotic gene activation, and mechanisms regulating embryonic stem
cell differentiation and maintenance of stem cell pluripotency.
o Reproductive Tract Biology and Physiology -- folliculogenesis, including
studies addressing intraovarian control of follicle selection and atresia by
growth factors, cytokines, and their respective binding proteins and receptor
antagonists, luteogenesis and luteolysis, including intraovarian mechanisms
that control luteal life span, implantation, including cell-to-cell
interactions regulating implantation, structure, function, and regulation of
the epididymis.
o Reproductive Endocrinology and Neuroendocrinology -- fundamental
mechanisms of hormone synthesis, secretion, regulation, and action in the
context of reproduction, including intrapituitary mechanisms governing
gonadotropin secretion, and intraneuronal mechanisms and glia-neuron
interactions controlling pulsatile GnRH secretion, identification of elements
and factors controlling gene transcription including co-activators and co-
repressors, and identification of signaling molecules and pathways mediating
hormone action, interaction of the immune and neuroendocrine systems in
controlling fertility, mechanisms by which nutritional modification alters
the hypothalamo-pituitary-gonadal endocrine axis.
o Reproductive Genetics -- genetics of sex determination including
clarification of the functional interactions between the known sex
determination genes, role of inheritance and expression of parental alleles
in reproduction including genes and mechanisms important in imprinting and
methylation during gametogenesis and embryogenesis, and elucidation of the
genes and genetic mechanisms responsible for normal and skewed X chromosome
inactivation.
o Reproductive Medicine -- etiology, pathophysiology, prevention, diagnosis
and treatment of male or female infertility with particular emphasis on
defining those conditions which are genetically based, relation of
endometriosis to infertility, treatment of benign gynecologic diseases,
research leading to improved outcomes across the spectrum of assisted
reproductive technologies, as well as development of new approaches for
assisted reproduction.
Because this list is not meant to be all-inclusive, prospective applicants
preparing either a new or competing continuation center grant application are
encouraged to discuss program relevance issues with the program staff contact
cited under WHERE TO SEND INQUIRIES, below. However, applicants should note
that the research scope of this RFA does not include studies in the area of
reproductive oncology, reproductive toxicology or reproductive epidemiology
or studies dealing with post-implantation pregnancy and parturition. These
topic areas are outside the scope of research supported by the RSB and,
therefore, will be deemed non-responsive to this RFA. Further, applications
proposing research activities focused exclusively on clinical research or
exclusively on basic research, or applications or components thereof
proposing epidemiological or large-scale clinical trial research, will not be
considered responsive to this RFA.
Guidance and Management Structures
Overall coordination of the Centers Program, consistent with the stated
objectives set forth in this RFA (see Objectives), will be done by a Steering
Committee consisting of all Center Principal Investigators and an NICHD Staff
Research Coordinator from the RSB, CPR. The Steering Committee will employ a
consensus decision process to guide the Centers Program in evaluating the
progress of member Center programs, their proposed new research initiatives
within the general scope of the approved program, the need to provide the
entire Center network with access to new technologies, the need for
collaborations either within or outside the Center network, and the need to
redirect certain efforts of member Centers due to either sufficient data
acquisition to permit conclusion, the acquisition of data supporting an
alternative study initiative or experience proving that the proposed research
is no longer feasible.
In addition to the Steering Committee, smaller cooperative groups will be
formed that consist of research components of member centers having common
research interests addressing a specific basic and/or clinical research
problem. These research focus groups will perform coordinated research
activities as recommended by the Steering Committee. In turn, progress of
the focus groups will further guide the Steering Committee in decision-making
regarding changes in specific research directions, translational activities,
and collaborative research initiatives. The research focus group will
consist of an NICHD Staff Research Coordinator from the RSB, CPR, and Key
Investigators of the relevant subproject and/or Core Directors.
Further details of the guidance and management structures and processes may
be found under "Cooperative Agreement Terms and Conditions of Award," below.
MECHANISM OF SUPPORT
This RFA will use the NIH Specialized Cooperative Research Center (U54) award
mechanism. As an applicant you will be solely responsible for planning,
directing, and executing the proposed project. At this time, the NICHD plans
to reissue this RFA on an annual basis. The anticipated award date is April
1, 2004.
The NIH U54 is a cooperative agreement award mechanism in which the Principal
Investigator retains the primary responsibility and dominant role for
planning, directing, and executing the proposed project, with NIH staff being
substantially involved as a partner with the Principal Investigator, as
described under the section "Cooperative Agreement Terms and Conditions of
Award."
FUNDS AVAILABLE
The NICHD intends to commit approximately $4.9 million in total costs [Direct
plus Facilities and Administrative (F & A) costs] in FY 2004 to fund up to
four new and/or competing continuation grants in response to this RFA. An
applicant for a new center may request a project period of up to five years
and a budget for direct costs of up to $900,000 for the first year, excluding
F & A costs on consortium arrangements, with incremental increases for
recurring costs (i.e., personnel, consultants, supplies, travel and other
expenses) not to exceed three percent in each subsequent year. An applicant
for a competing continuation grant may request a project period of up to five
years and a budget for direct costs of up to $900,000 in the first year or
120 percent of the direct costs awarded for the final competitive segment of
the preceding project period as stated in the Notice of Grant Award,
whichever is higher. Applications exceeding the budgetary limits specified
above will be returned to the applicant without peer review. Because the
nature and scope of the research proposed may vary, it is anticipated that
the size of awards also will vary. Although the financial plans of NICHD
provide support for this program, awards pursuant to this RFA are contingent
upon the availability of funds and the receipt of a sufficient number of
meritorious applications.
In the event that an application submitted in response to this RFA is not
funded, one revision of the application may be submitted in response to a
subsequent RFA. Requested budgets for revised applications must follow the
recommendations of the peer review group who evaluated the initial submission
unless the submission of a different budget request has been authorized in
advance by the NICHD. If a revised competing continuation application is not
selected for funding, the applicant institution may then submit only a new,
substantially different application in response to a subsequent RFA that will
be subject to the direct cost limit of $900,000.
ELIGIBLE INSTITUTIONS
You may submit an application if your institution has any of the following
characteristics:
o For-profit or non-profit organizations
o Public or private institutions, such as universities, colleges, hospitals,
and laboratories
o Units of State and local governments
o Eligible agencies of the Federal government
o Domestic. Foreign institutions are not eligible to apply as an applicant
institution, however, subcontracts from domestic entities to foreign sites
are permitted
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS
Any individual with the skills, knowledge, and resources necessary to carry
out the proposed research is invited to work with their institution to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH programs.
SPECIAL REQUIREMENTS
Description of a Center
The minimal requirements for a Center described in this RFA are as follows
(see sections on Review Procedures and Award Criteria below):
o A research plan that is responsive to the objectives of the Centers Program
set forth in this RFA (see RESEARCH OBJECTIVES).
o At least three research subprojects that thematically address one or more
research areas listed under Research Scope. It is required that at least one
subproject be entirely or predominantly clinical in nature. For the purpose
of this Centers Program, the definition of "clinical" includes studies that
involve patients or use of cultured human cells or tissue. Although not
required, it is strongly encouraged that at least one basic science
subproject be in a similar scientific area as the clinical subproject in
order to facilitate transfer of information from bench to bedside.
Alternatively, a project may be proposed that incorporates both basic and
clinical approaches to a particular problem.
o An administrative core unit that provides oversight to the Center, located
at the applicant institution and accessed only by budgeted Center subprojects
and cores.
o A competent and experienced Principal Investigator who is committed to and
directly involved in research dealing with mammalian reproduction.
o Availability of competent and experienced scientific experts to direct
individual research projects or cores associated with the proposed Center.
o Availability of the technical resources and facilities necessary for the
conduct of the research.
o Access to properly managed animal facilities for projects conducting
animal studies.
o As appropriate, access to inpatient and outpatient reproductive health
care units providing adequate numbers of patients for clinical research
projects that require patient participation. [Applications from institutions
that have a General Clinical Research Center (GCRC) funded by the NIH
National Center for Research Resources may wish to identify the GCRC as a
resource for conducting the proposed research. In such a case, a letter of
agreement from either the GCRC Program Director or Principal Investigator
should be included with the application.]
Optional components of the Center organization include the mix of subprojects
and cores to be included in the Center:
o The Principal Investigator may choose to organize the Center using
collaborations of projects within the same institution. Alternatively,
Centers may seek to maximize their scientific expertise and research
capabilities by including in the application a subproject and/or a technical
service core to be supported at other institutions through subcontracted
consortium arrangements. No more than one consortium subproject and one
consortium core service facility will be permissible in each Center.
o Funds may be requested to provide support for one or more pilot projects
relevant to the center"s goals. Support for a pilot project is limited to a
two-year period. Funding may not exceed 10 percent of the center grant"s
first-year direct cost budget, inclusive of the portion budgeted for pilot
projects, or $90,000 per year, whichever amount is smaller. With NICHD staff
approval, the period of support may be extended one additional year. Funds
for pilot projects may be requested in new or competing continuation
applications only. As such, the proposed research plan must be described in
sufficient detail, comparable to the other subprojects submitted in the
application, to permit evaluation of the project using the review criteria
listed under REVIEW CONSIDERATIONS. If a pilot project is favorably
recommended for an initial two-year period, funds will be included each year
for the full five years. Funds in Years 03-05 will be contingent upon review
and approval of additional pilot projects by NICHD staff. Funding levels in
these out-years will be based on the level of funding for this purpose in
Years 01 and 02.
o The Principal Investigator may choose one of two center structure options
regarding access to technical service core facilities.
Closed Access Structure - In this center structure, administrative and all
technical service cores will be utilized by budgeted center subprojects only.
Consistent with NICHD guidelines for establishment of core facilities,
utilization by three subprojects is required to justify a core technical
service facility. Percent utilization by any one of the three subprojects
justifying the core may not exceed 50 percent or be less than five percent.
The percent utilization of additional subprojects requiring core services may
be less than five percent. Costs necessary to use a particular core facility
may be incorporated into the budget of the core unit, and not in the budgets
of the research subprojects per se. No internal charge-back system would be
required.
Open Access Structure - In this center structure, budgeted center subprojects
as well as research projects external to the Center (e.g., R01, R03, P01
subproject) may have access to technical service cores. However, special
consideration must be given to justification of a technical service core
facility and the formal establishment of an effective charge-back system for
all technical service cores. For each core service facility, at least one of
the three projects used to justify a core must be a budgeted center
subproject, while the remaining project(s) used in justifying the core must
be externally funded NICHD projects administered by the RSB. Percent
utilization by any internally budgeted center subproject or externally-funded
RSB project used to justify a particular core facility may not exceed 50
percent or be less than five percent. An additional seven federally-funded,
peer-reviewed external research projects addressing program-relevant research
areas of the RSB may access the core up to 100 percent of its service
capacity. The 50/5 percent utilization requirement applies to this group of
external projects. Centers must establish an internal management policy for
evaluating the acceptability of proposed RSB program relevant external
projects to access the core facilities. Approval of requests for core access
privileges for external projects which would replace those described above
must be made to RSB Program Staff who then will evaluate the extent to which
the project is relevant to RSB mission research areas (see Research Scope),
and render a decision accordingly.
If centers choose to operate in an open access format, costs necessary to
utilize a particular core facility by budgeted center subprojects must be
incorporated into the budget of the subproject and not the core budget in
order to accommodate participation in the required charge-back system. Core
budgets will be justified and evaluated based on access by budgeted center
subprojects and external, program-relevant research projects as described
above. Above and beyond this arrangement, technology-based core units may
offer services to additional external projects addressing any area of
research regardless of funding source only on a full payback (fee-for-service
or in-kind) basis. However, additional funds necessary to provide services
to these external projects (e.g., technical support, supplies, etc.) must
come from sources other than the center funding, such as the supply budgets
of the external projects wishing to access the core facilities. In choosing
to configure a center in an open-access center structure, the Principal
Investigator must have in place, and adequately describe in the application,
management policies that ensure that budgeted center subprojects are given
highest priority in receiving services provided by the core.
Centers choosing to configure in an open-access center format may propose one
or more technical service cores that will be utilized exclusively by budgeted
center subprojects. These centers may, therefore, have a mix of open and
restricted access technical service cores. On the other hand, administrative
cores in open center structures may be accessed only by budgeted center
subprojects.
Once an award is made, centers configured as a closed-access center structure
may, at a later time, choose to convert to an open access center structure by
requesting such conversion in writing to the NICHD.
Travel to Meetings
Principal Investigators should request travel funds to support their
participation in the annual Steering Committee Meeting as well as one
research focus group meeting. Key Investigators of budgeted center
subprojects and Directors of technical service cores should request travel
funds to support participation in two research focus group meetings.
Cooperative Agreement Terms and Conditions of Award
Cooperative agreements are assistance mechanisms and are subject to the same
administrative requirements as grants. The following Terms and Conditions of
Award are in addition to, and not in lieu of, otherwise applicable OMB
administrative guidelines, HHS and NIH grant regulations, policies and
procedures, with particular emphasis on HHS regulations at 45 CFR Part 74 and
92. Business management aspects of these awards will be administered by the
NICHD Grants Management Branch in accordance with HHS and NIH grant
administration requirements.
The purpose of these cooperative agreements is to support a coordinated
research program of specialized centers pursuing high quality reproductive
research with the ultimate goal of facilitating and accelerating translation
of basic science knowledge into clinical applications that can be used to
regulate fertility or diagnose and treat infertility or reproductive
disorders that impact on fertility.
1. Awardee Rights and Responsibilities
The primary authorities and responsibilities of the awardees are to
participate cooperatively with the Steering Committee in the following
activities:
o Pursue research objectives consistent with the research scope of the RFA
and research favorably recommended by peer review,
o Conduct experiments and collect the resulting data,
o Analyze, interpret and present results and plans to the Steering Committee
for approved activities,
o Publish results, conclusions, and interpretation of the studies.
The awardees will agree to: 1) accept the coordinating role of the Steering
Committee which includes evaluating objectives and research goals of the
Centers Program, and recommending modification, deletion or addition of
protocols within the Centers Program, 2) follow any common protocols in which
they participate for multicenter projects that are approved by the Steering
Committee, and 3) accept the cooperative nature of the group process,
including the establishment, where appropriate, of smaller collaborative
groups comprised of interacting subprojects and/or cores focused on a
particular reproductive research topic area.
Awardees will retain custody of and primary rights to their data developed
under the award subject to current government policies regarding rights of
access as consistent with current DHHS and NIH policies.
2. NICHD Responsibilities
NICHD Research Coordinator:
o Participating in the overall coordination of the Centers Program with the
Steering Committee. This includes efforts to improve and strengthen inter-
and intra-center cooperation amongst the research projects of the Centers,
particularly as it pertains to translational research activities within and
between centers. As a means of improving inter-center cooperation, the
Research Coordinator will directly participate in the activities of the
smaller collaborative groups established by the Steering Committee comprising
subprojects and/or cores focused on a particular reproductive research topic
area. The Research Coordinator will also assist the research efforts of the
Centers Program by facilitating access to fiscal and intellectual resources
provided by industry, private foundations and NIH intramural scientists. The
Research Coordinator will, as required, help reprogram research efforts,
including options to modify or terminate them, by mutual consent between the
Centers Program and NICHD. In the event of disagreements among the Program
participants, the Research Coordinator will assist in forming an arbitration
panel as discussed below.
o Interacting with each individual center awardee evaluating objectives and
research goals of that particular center, deciding optimal research
approaches and protocol designs, and contributing to the adjustment of
research protocols or approaches as warranted. The Research Coordinator will
assist and facilitate this process and not direct it. The Research
Coordinator will also provide assistance in reviewing and commenting on all
major transitional changes of an individual center"s activities prior to
implementation to assure consistency with required goals of the Centers
Program.
o Retaining the option to recommend the withholding of support from a Center
subproject or core materially failing to meet the technical performance
requirements established by the Centers Program. This includes identifying
jointly with participants of the Steering Committee the need to add
additional research subprojects or service cores to Centers or to phase out a
Center subproject or core when performance standards have not been met, and
o Participating, where warranted, in data analyses, interpretations, and the
dissemination of study findings to the research community and health care
recipients including co- authorship of the publication of results of studies
conducted by the Centers.
NICHD Project Officer:
NICHD will appoint a Project Officer, apart from the Research Coordinator,
who will:
o Have the option to withhold support to a participating institution if
technical performance requirements are not met,
o Carry out continuous review of all activities to ensure objectives are
being met, and
o Exercise the normal stewardship responsibilities of an NIH Program
Officer.
3. Collaborative Responsibilities
Overall Coordination of the Centers Program consistent with the stated intent
of the RFA will be done by a Steering Committee consisting of the Principal
Investigators from each of the participating Centers and one NICHD staff
member from the RSB, CPR, NICHD, who will be the Research Coordinator. A
member of the NICHD grants management staff will serve as a nonvoting advisor
to the Committee. A chairperson for the Steering Committee will be chosen by
a majority vote of the Principal Investigators. The Steering Committee
meetings will be convened at least once per year. The purpose of these
meetings is to share scientific information, assess scientific progress,
identify new research opportunities and potential avenues of collaborations
such as with industry, private foundations and/or NIH intramural scientists,
establish priorities that will accelerate the translation of preclinical
findings into clinical applications, reallocate resources and conduct the
business of the cooperative research program. In anticipation that some
centers will have common research interests that address a specific basic
and/or clinical research problem, it is envisioned that research focus groups
will be formed to conduct coordinated research activities recommended by the
Steering Committee. The Steering Committee will approve multicenter
protocols on specific research activities. As needed, the Steering Committee
will develop a publication policy regarding joint authorship of research
reports derived from such collaborative efforts.
4. Arbitration
When agreement between an awardee and NICHD staff cannot be reached on
scientific/programmatic issues that may arise after the award, an arbitration
panel will be formed. The panel will consist of one person selected by the
Principal Investigator, one person selected by NICHD staff, and a third
person selected by these two members. The decision of the arbitration panel,
by majority vote, will be binding. This special arbitration procedure in no
way affects the right of an awardee to appeal an adverse action in accordance
with PHS regulations at 42 CFR Part 50, Subpart D, and DHHS regulations at 45
CFR Part 16.
WHERE TO SEND INQUIRIES
We encourage inquiries concerning this RFA and welcome the opportunity to
answer questions from potential applicants. Inquiries may fall into three
areas: scientific/research, peer review, and financial or grants management
issues:
o Direct your questions about scientific/research issues to:
Louis V. DePaolo, Ph.D.
Reproductive Sciences Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8B01, MSC 7510
Bethesda, MD 20892-7510
Telephone: (301) 435-6970
FAX: (301) 496-0962
E-mail: ld38p@nih.gov
o Direct your questions about peer review issues to:
Robert Stretch, Ph.D.
Director, Division of Scientific Review
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 5B01, MSC 7510
Bethesda, MD 20892-7510
Telephone: (301) 496-1485
Email: stretch@nih.gov
o Direct your questions about financial or grants management matters to:
Ms. Kathy Hancock
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A17M, MSC 7510
Bethesda, MD 20892-7510
Telephone: (301) 496-5482
FAX: (301) 480-4782
E-mail: kh47d@nih.gov
LETTER OF INTENT
Prospective applicants are asked to submit a letter of intent that includes
the following information:
o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel
o Participating institutions
o Number and title of this RFA
Although a letter of intent is not required, is not binding, and does not
enter into the review of a subsequent application, the information that it
contains allows NICHD staff to estimate the potential review workload and
plan the review.
The letter of intent is to be sent by the date listed at the beginning of
this document. The letter of intent should be sent to:
Louis V. DePaolo, Ph.D.
Reproductive Sciences Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8B01, MSC 7510
Bethesda, MD 20892-7510
Telephone: (301) 435-6970
FAX: (301) 496-0962
E-mail: ld38p@nih.gov
SUBMITTING AN APPLICATION
Applications must be prepared using the PHS 398 research grant application
instructions and forms (rev. 5/2001). The PHS 398 is available at
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive
format. For further assistance contact GrantsInfo, Telephone (301) 435-0714,
Email: GrantsInfo@nih.gov.
SUPPLEMENTAL INSTRUCTIONS: Applications for the U54 grant are to be prepared
in a manner consistent with the information presented in the NICHD U54
Cooperative Specialized Research Center Grant Guidelines, available from the
contacts listed under INQUIRIES, below, and at
http://www.nichd.nih.gov/funding/mechanism/u54_guide.cfm.
At minimum, an application in response to this RFA should include:
o A description of a Specialized Center in Reproduction Research consisting
of multiple individual research subprojects, an Administrative Core and, if
applicable, one or more technology-based core service facilities.
o A description of the capabilities of the Center to meet or exceed the
minimal requirements for a Center stated in this RFA (see Description of a
Center).
o A proposed five-year research plan that presents the applicant"s
perception of the Center"s organization and component functions. This plan
should demonstrate the applicant"s knowledge, ingenuity, practicality, and
commitment in organizing a multi-project research infrastructure for
conducting basic and clinical studies in the reproductive sciences. The
research plan for the Center and all component subprojects must address the
"Research Scope" described above.
o A statement describing the willingness of the Principal Investigator to
cooperate in a coordinated cooperative program involving multiple Centers
with the objective of developing research project and/or service core
interactions between Centers.
o Substantive evidence of departmental and institutional support for and
commitment to the proposed Center.
o For competing renewal applications, evidence of having met the Terms and
Conditions of the award during the previous funding period.
All applicants must document their ability to meet or exceed the minimum
requirements as set forth in this RFA. This specifically includes
understanding of and commitment to the cooperative nature of this Program,
and willingness to meet the Terms and Conditions of Award.
USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 5/2001)
application form must be affixed to the bottom of the face page of the
application. Type the RFA number on the label. Failure to use this label
could result in delayed processing of the application such that it may not
reach the review committee in time for review. In addition, the RFA title
and number must be typed on line 2 of the face page of the application form
and the YES box must be marked. The RFA label is also available at:
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of
the application, including the Checklist, and three signed, photocopies, in
one package to:
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710
Bethesda, MD 20817 (for express/courier service)
At the time of submission, two additional copies of the application must be
sent to:
Robert Stretch, Ph.D.
Director, Division of Scientific Review
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 5B01, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service)
APPLICATION PROCESSING: Applications must be received by the application
receipt date listed in the heading of this RFA. If an application is
received after that date, it will be returned to the applicant without
review.
The Center for Scientific Review (CSR) will not accept any application in
response to this RFA that is essentially the same as one currently pending
initial review, unless the applicant withdraws the pending application. The
CSR will not accept any application that is essentially the same as one
already reviewed. This does not preclude the submission of substantial
revisions of applications already reviewed, but such applications must
include an Introduction addressing the previous critique. Only one revision
of a new or competing continuation application submitted in response to this
RFA may be submitted in response to a subsequent RFA.
PEER REVIEW PROCESS
Upon receipt, applications will be reviewed for completeness by CSR and for
responsiveness to the RFA by NICHD staff. Incomplete and/or non-responsive
applications will be returned to the applicant without further consideration.
Any application that does not meet the minimum application requirements as
set forth under SPECIAL REQUIREMENTS will be considered unresponsive to the
RFA. Responsiveness includes, but is not limited to, the program relevance
of the proposed research subprojects and external projects being proposed to
access core facilities, as determined by NICHD.
Applications that are complete and responsive to the RFA will be evaluated
for scientific and technical merit by an appropriate peer review group
convened by the NICHD in accordance with the review criteria stated below.
As part of the initial merit review, all applications will:
o Receive a written critique
o Undergo a process in which only those applications deemed to have the
highest scientific merit, generally the top half of the applications under
review, will be discussed and assigned a priority score
o Receive a second level review by the National Advisory Child Health and
Human Development Council
A site visit will not be part of the review process. Applicants should
ensure that their applications are complete as written and can stand on their
own.
REVIEW CRITERIA
The scientific and technical merit peer review focuses on three areas: (1)
review of the component research subprojects, (2) review of the core units,
and (3) review of the overall center as an integrated effort. Applications
submitted in response to this RFA will be evaluated according to the review
criteria described in the NICHD U54 Cooperative Specialized Research Center
Grant Guidelines, available from the contacts listed under INQUIRIES, below,
and at http://www.nichd.nih.gov/funding/mechanism/u54_guide.cfm.
RECEIPT AND REVIEW SCHEDULE
Letter of Intent Receipt Date: May 21, 2003
Application Receipt Date: June 18, 2003
Peer Review Date: October/November 2003
Council Review: January 2004
Earliest Anticipated Start Date: April 1, 2004
AWARD CRITERIA
Award criteria that will be used to make award decisions include:
o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities.
REQUIRED FEDERAL CITATIONS
INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of
the NIH that women and members of minority groups and their sub-populations
must be included in all NIH-supported clinical research projects unless a
clear and compelling justification is provided indicating that inclusion is
inappropriate with respect to the health of the subjects or the purpose of
the research. This policy results from the NIH Revitalization Act of 1993
(Section 492B of Public Law 103-43).
All investigators proposing clinical research should read the AMENDMENT "NIH
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical
Research - Amended, October, 2001," published in the NIH Guide for Grants and
Contracts on October 9, 2001 (
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html), a complete
copy of the updated Guidelines is available at
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical
research, updated racial and ethnic categories in compliance with the new OMB
standards, clarification of language governing NIH-defined Phase III clinical
trials consistent with the new PHS Form 398, and updated roles and
responsibilities of NIH staff and the extramural community. The policy
continues to require for all NIH-defined Phase III clinical trials that: a)
all applications or proposals and/or protocols must provide a description of
plans to conduct analyses, as appropriate, to address differences by
sex/gender and/or racial/ethnic groups, including subgroups if applicable,
and b) investigators must report annual accrual and progress in conducting
analyses, as appropriate, by sex/gender and/or racial/ethnic group
differences.
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS:
The NIH maintains a policy that children (i.e., individuals under the age of
21) must be included in all human subjects research, conducted or supported
by the NIH, unless there are scientific and ethical reasons not to include
them. This policy applies to all initial (Type 1) applications submitted for
receipt dates after October 1, 1998.
All investigators proposing research involving human subjects should read the
"NIH Policy and Guidelines" on the inclusion of children as participants in
research involving human subjects that is available at
http://grants.nih.gov/grants/funding/children/children.htm.
REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH
policy requires education on the protection of human subject participants for
all investigators submitting NIH proposals for research involving human
subjects. You will find this policy announcement in the NIH Guide for Grants
and Contracts Announcement, dated June 5, 2000, at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research
on hESCs can be found at http://grants.nih.gov/grants/stem_cells.htm and at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only
research using hESC lines that are registered in the NIH Human Embryonic Stem
Cell Registry will be eligible for Federal funding (see http://escr.nih.gov).
It is the responsibility of the applicant to provide the official NIH
identifier(s)for the hESC line(s)to be used in the proposed research.
Applications that do not provide this information will be returned without
review.
PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The
Office of Management and Budget (OMB) Circular A-110 has been revised to
provide public access to research data through the Freedom of Information Act
(FOIA) under some circumstances. Data that are (1) first produced in a
project that is supported in whole or in part with Federal funds and (2)
cited publicly and officially by a Federal agency in support of an action
that has the force and effect of law (i.e., a regulation) may be accessed
through FOIA. It is important for applicants to understand the basic scope
of this amendment. NIH has provided guidance at
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this RFA in a public
archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application should
include a description of the archiving plan in the study design and include
information about this in the budget justification section of the
application. In addition, applicants should think about how to structure
informed consent statements and other human subjects procedures given the
potential for wider use of data collected under this award.
URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals
for NIH funding must be self-contained within specified page limitations.
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs)
should not be used to provide information necessary to the review because
reviewers are under no obligation to view the Internet sites. Furthermore,
we caution reviewers that their anonymity may be compromised when they
directly access an Internet site.
HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to
achieving the health promotion and disease prevention objectives of "Healthy
People 2010," a PHS-led national activity for setting priority areas. This
RFA is related to one or more of the priority areas. Potential applicants may
obtain a copy of "Healthy People 2010" at
http://www.health.gov/healthypeople.
AUTHORITY AND REGULATIONS: This program is described in the Catalog of
Federal Domestic Assistance No. 93.864, Population Research, and is not
subject to the intergovernmental review requirements of Executive Order 12372
or Health Systems Agency review. Awards are made under authorization of
Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241
and 284) and administered under NIH grants policies described at
http://grants.nih.gov/grants/policy/policy.htm and under Federal Regulations
42 CFR 52 and 45 CFR Parts 74 and 92.
The PHS strongly encourages all grant recipients to provide a smoke-free
workplace and discourage the use of all tobacco products. In addition,
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in
certain facilities (or in some cases, any portion of a facility) in which
regular or routine education, library, day care, health care, or early
childhood development services are provided to children. This is consistent
with the PHS mission to protect and advance the physical and mental health of
the American people.